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Semin Liver Dis 2004; 24: 45-53
DOI: 10.1055/s-2004-828678
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Treatment with Interferons (including Pegylated Interferons) in Patients with Hepatitis B

W. Graham Cooksley1
  • 1Department of Medicine, The University of Queensland, Royal Brisbane Hospital, Queensland, Australia
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Publikationsverlauf

Publikationsdatum:
11. Juni 2004 (online)

    Lizenzen und Reprints

Studies of 4 to 6 months of treatment with interferon for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection have shown clearance of HBeAg to be higher in treated patients than it is in controls by approximately 25%. These results are considerably better than those with antiviral agents. Therefore, the recent European Association for the Study of the Liver (EASL) Consensus Committee recommended the use of interferon α for this condition. Treatment with pegylated interferons in several trials has shown better results still. Lamivudine in combination with interferon, however, did not improve the results at 6 months after the end of therapy. In HBeAg-negative chronic HBV infection, pegylated interferon α is superior to lamivudine, and, again, combination with lamivudine does not improve the results. Side effects in all studies have been tolerable. Thus, these observations in chronic HBV infection, whether HBeAg-positive or HBeAg-negative, suggest an important, even primary, role for pegylated interferon therapy.

KEYWORDS

Interferon - pegylated interferon alfa-2a (40 kD) - pegylated interferon alfa-2b (12 kD)

REFERENCES

  • 1 Greenberg H B, Pollard R B, Lutwick L I et al.. Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis.  N Engl J Med. 1976;  295 517-522
    PubMedSuche in Google Scholar
  • 2 Lok A S, Heathcote E J, Hoofnagle J H. Management of hepatitis B: 2000. Summary of a workshop.  Gastroenterology. 2001;  120 1828-1853
    PubMedSuche in Google Scholar
  • 3 EASL International Consensus Conference on Hepatitis B . 13-14 September, 2002: Geneva, Switzerland. Consensus statement (short version).  J Hepatol. 2003;  38 533-540 , (review)
    CrossrefPubMedSuche in Google Scholar
  • 4 Manns M P. Current state of interferon therapy in the treatment of chronic hepatitis B.  Semin Liver Dis. 2002;  22(Suppl 1) 7-13
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Conjeevaram H S, Lok A S-F. Management of chronic hepatitis B.  J Hepatol. 2003;  38 S90-S103
    PubMedSuche in Google Scholar
  • 6 Cooksley W G. Treatment of hepatitis B with interferon and combination therapy.  Clin Liver Dis N Am. 2004;  , (In press)
    PubMedSuche in Google Scholar
  • 7 Wong D K, Cheung A M, O'Rourke K et al.. Effect of α-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.  Ann Intern Med. 1993;  119 312-323
    PubMedSuche in Google Scholar
  • 8 Craxi A, Di Bona D, Camma C. Interferon alpha for HBeAg positive chronic hepatitis B: systematic review.  J Hepatol. 2003;  39(Suppl 1) 99-105
    PubMedSuche in Google Scholar
  • 9 Bortolotti F, Jara P, Barbera C et al.. Long term effect of alpha interferon in children with chronic hepatitis B.  Gut. 2000;  46 715-718
    CrossrefPubMedSuche in Google Scholar
  • 10 Fattovich G, Giustina G, Sanchez-Tapias J et al.. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP).  Am J Gastroenterol. 1998;  93 896-900
    CrossrefPubMedSuche in Google Scholar
  • 11 Lau D T, Everhart J, Kleiner D E et al.. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa.  Gastroenterology. 1997;  113 1660-1667
    PubMedSuche in Google Scholar
  • 12 Lin S M, Sheen I S, Chien R N et al.. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection.  Hepatology. 1999;  29 971-975
    CrossrefPubMedSuche in Google Scholar
  • 13 Lok A S, Chung H T, Liu V W, Ma O C. Long-term follow-up of chronic hepatitis B patients treated with interferon alfa.  Gastroenterology. 1993;  105 1833-1838
    PubMedSuche in Google Scholar
  • 14 Lok A SF, McMahon B J. Chronic hepatitis B.  Hepatology. 2001;  34 1225-1241
    CrossrefPubMedSuche in Google Scholar
  • 15 Krogsgaard K. The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B. The Long-Term Follow-up Investigator Group. The European Study Group on Viral Hepatitis (EURHEP) Executive Team on Anti-Viral Treatment.  J Viral Hepat. 1998;  5 389-397
    CrossrefPubMedSuche in Google Scholar
  • 16 Thomas H C, Lok A SF, Carreno V et al.. Comparative study of three doses of interferon alfa-2a in chronic active hepatitis B. The International Hepatitis Trial Group.  J Viral Hepat. 1994;  1 139-148
    PubMedSuche in Google Scholar
  • 17 Janssen H L, Gerken G, Carreno V et al.. Interferon alpha for chronic hepatitis B infection: increased efficacy of prolonged treatment. The European Concerted Action on Viral Hepatitis (EUROHEP).  Hepatology. 1999;  30 238-243
    CrossrefPubMedSuche in Google Scholar
  • 18 Cohard M, Poynard T, Mathurin P et al.. Prednisone-interferon combination in the treatment of chronic hepatitis B: direct and indirect meta-analysis.  Hepatology. 1994;  20 1390-1398
    CrossrefPubMedSuche in Google Scholar
  • 19 Kao J H, Wu N H, Chen P J et al.. Hepatitis B genotypes and the response to interferon therapy.  J Hepatol. 2000;  33 998-1002
    CrossrefPubMedSuche in Google Scholar
  • 20 Zhang X, Zoulim F, Habersetzer F et al.. Analysis of hepatitis B virus genotypes and pre-core region variability during interferon treatment of HBe antigen negative chronic hepatitis B.  J Med Virol. 1996;  48 8-16
    CrossrefPubMedSuche in Google Scholar
  • 21 Hoofnagle J H, Di Bisceglie A M, Waggoner J G, Park Y. Interferon alfa for patients with clinically apparent cirrhosis due to chronic hepatitis B.  Gastroenterology. 1993;  104 1116-1121
    PubMedSuche in Google Scholar
  • 22 Perrillo R, Tamburro C, Regenstein F et al.. Low-dose, titratable interferon alfa in decompensated liver disease caused by chronic infection with hepatitis B virus.  Gastroenterology. 1995;  109 908-916
    PubMedSuche in Google Scholar
  • 23 Janssen H L, Schalm S W, Berk L et al.. Repeated courses of alpha-interferon for treatment of chronic hepatitis type B.  J Hepatol. 1993;  17(Suppl 3) S47-S51
    PubMedSuche in Google Scholar
  • 24 Carreno V, Marcellin P, Hadziyannis S et al.. Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP).  Hepatology. 1999;  30 277-282
    CrossrefPubMedSuche in Google Scholar
  • 25 Manesis E K, Hadziyannis S J. Interferon alpha treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B.  Gastroenterology. 2001;  121 101-109
    CrossrefPubMedSuche in Google Scholar
  • 26 Brunetto M R, Oliveri F, Coco B et al.. The outcome of chronic anti-HBe positive chronic hepatitis B in alpha interferon treated and untreated patients: a long term cohort study.  J Hepatol. 2002;  36 263-270
    PubMedSuche in Google Scholar
  • 27 Lampertico P, Del Ninno E, Manzin A et al.. A randomized controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum.  Hepatology. 1997;  26 1621-1625
    PubMedSuche in Google Scholar
  • 28 Papatheodoridis G V, Manesis E, Hadziyannis S J. The long term outcome of interferon-alpha treated and untreated patients with HBeAg-negative chronic hepatitis B.  J Hepatol. 2001;  34 306-313
    CrossrefPubMedSuche in Google Scholar
  • 29 Oliveri F, Santantonio T, Bellati G et al.. Long term response to therapy of chronic anti-HBe-positive hepatitis B is poor independent of type and schedule of interferon.  Am J Gastroenterol. 1999;  94 1366-1372
    PubMedSuche in Google Scholar
  • 30 Cooksley W GE, Lai M-Y, Piratvisuth T et al.. Peginterferon a-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B.  J Viral Hepat. 2003;  10 298-305
    CrossrefPubMedSuche in Google Scholar
  • 31 Cooksley W GE, Lai M-Y, Piratvisuth T et al.. Treatment with peginterferon alfa-2a (40kD) (Pegasys) results in improved rates of response compared to conventional interferon in patients with HBeAg positive chronic hepatitis B, including HBV genotypes B or “difficult to treat” genotype C.  J Hepatol. 2003;  38 52 , (abst)
    PubMedSuche in Google Scholar
  • 32 Niederau C, Heintges T, Lange S et al.. Long-term follow-up HBeAg-positive patients treated with interferon alfa for chronic hepatitis B.  N Engl J Med. 1996;  334 1422-1427
    CrossrefPubMedSuche in Google Scholar
  • 33 Liaw Y-F, Chow W C, Shue K et al.. Effects of lamivudine on disease progression and development of liver cancer in advanced chronic hepatitis B: a prospective double-blind placebo-controlled clinical trial.  Hepatology. 2003;  38(Suppl 1) 262A
    PubMedSuche in Google Scholar
  • 34 Hadziyannis S, Tassopoulos N, Heathcote J et al.. 96 weeks of adefovir dipivoxil in HBeAg negative chronic hepatitis B: significant virological, biochemical and histological improvement. Presented at the 11th International Symposium on Viral Hepatitis in Liver Disease April 5-8, 2003 Sydney, Australia;
    Suche in Google Scholar
  • 35 Chang T T, Lim S G, Hadziyannis S et al.. Long-term safety of adefovir dipivoxil 10 mg once daily in chronic hepatitis B: an integrated analysis of two phase III studies.  J Hepatol. 2003;  38(Suppl 2) 133A
    PubMedSuche in Google Scholar
  • 36 Mutimer D, Naoumov N, Honkoop P et al.. Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.  J Hepatol. 1998;  28 923-929
    CrossrefPubMedSuche in Google Scholar
  • 37 Schiff E R, Karayalcin S, Grimm I et al.. A placebo controlled study of lamivudine and interferon α-2b in patients with chronic hepatitis B who previously failed interferon therapy.  Hepatology. 1998;  28 388A
    PubMedSuche in Google Scholar
  • 38 Schalm S W, Heathcote J, Cianciara J et al.. Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial.  Gut. 2000;  46 562-568
    CrossrefPubMedSuche in Google Scholar
  • 39 Barbaro G, Zechini F, Pellicefli A M et al.. Long-term efficacy of alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with hepatitis B. An Italian multicenter randomized trial.  J Hepatol. 2001;  35 406-411
    CrossrefPubMedSuche in Google Scholar
  • 40 Sanantonio T, Niro G A, Sinisi E et al.. Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B: a controlled pilot study.  J Hepatol. 2002;  36 799-804
    CrossrefPubMedSuche in Google Scholar
  • 41 Sung J JY, Chan H LY, Hui A Y et al.. Combination of pegylated interferon and lamivudine is superior to lamivudine monotherapy in the treatment of chronic hepatitis B-a randomized trial.  J Hepatol. 2003;  38(Suppl 2) 33A
    PubMedSuche in Google Scholar
  • 42 Janssen H LA, Senturk H, Zeuzum S et al.. Peginterferon alfa-2b and lamivudine combination therapy compared with peginterferon alfa-2b for chronic HBeAg-positive hepatitis B: a randomized controlled trial in 307 patients.  Hepatology. 2003;  38(Suppl 1) 246A
    PubMedSuche in Google Scholar
  • 43 Marcellin P, Lau G KK, Bonino F et al.. A phase III, partially double-blinded study evaluating the efficacy and safety of peginterferon alfa-2A (40kD) (Pegasys®) alone or in combination with lamvudine vs lamivudine in 546 patients with HBeAg-negative/anti-HBe-positive chronic hepatitis B.  Hepatology. 2003;  38(Suppl 1) 724A
    PubMedSuche in Google Scholar
  • 44 Fried M W, Shiffman M L, Reddy K R et al.. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.  N Engl J Med. 2002;  347 975-982
    CrossrefPubMedSuche in Google Scholar

 Professor
Graham Cooksley

Department of Medicine, The University of Queensland

C8 Clinical Sciences Building, Royal Brisbane Hospital

Queensland, Australia 4029

eMail: grahamC@qimr.edu.au